AVELOX

 

  Avelox
  Moxifloxacin
  Bayer A. G
  NDA  021085, 021334
  Latest Package Insert
  Avelox 1999, 2003, 2004 2007
  Safety Profile
  Still in use
  DO NOT USE 

The European Medicines Agency has recommended limiting the use of oral moxifloxacin
At its July 2008 meeting, the agency's Committee for Medicinal Products for Human Use (CHMP) concluded that the benefits of oral moxifloxacin medicines continued to outweigh its risks.
However, due to safety concerns, mainly related to an increased risk of adverse hepatic reactions, it recommended restricting their use in these indications. (read more)

 DEAR DOCTOR LETTERS SENT REGARDING SEVERE ADRS TO AVELOX

FRANKFURT, Feb 14, 2008 (Reuters) - Bayer (BAYG.DE: Quote, Profile, Research) is sending letters warning doctors in Europe of rare incidents of severe liver and skin side effects in patients taking its Avelox antibiotic, the German drugs and chemicals group said on Thursday.

Bayer has included the additional warnings in the packaging of Avelox products since autumn last year after some incidents of severe side effects were monitored, but is now reinforcing this by writing to doctors.

"The side effects are very rare. But when it happens, it is quite severe to patients. We want doctors to be more aware," said Yvonne Moeller, a spokeswoman at Bayer.

Avelox, one of Bayer's top-selling drugs, saw sales of almost 400 million euros ($584.4 million) in 2006.

© Reuters 2008 All rights reserved

Original "Dear Doctor Letter" can be viewed by clicking here

This is a copy of the European Dear Doctor Letter

February 2008
IMPORTANT INFORMATION REGARDING SERIOUS ADVERSE REACTIONS AND SAFETY MEASURES
Direct Healthcare Professional Communication regarding moxifloxacin (Avelox®) and serious hepatic and bullous skin reactions
Dear Healthcare Professional,

In agreement with EU regulatory authorities, including the Medicines and Healthcare products Regulatory Agency (MHRA), Bayer would like to inform you of important safety information. A recent assessment of adverse reactions associated with the use of moxifloxacin resulted in the following information and recommendations:

• Treatment with moxifloxacin is associated with a risk of developing fulminant hepatitis potentially leading to life threatening liver failure and risk of potentially life threatening bullous skin reactions like Stevens-Johnson-Syndrome (SJS) or toxic epidermal necrolysis (TEN).
• Due to limited clinical data, moxifloxacin is contraindicated in patients with impaired liver function (Child Pugh C) and in patients with transaminases increased > 5 fold the upper limit of normal (ULN).
• Patients should be advised to stop treatment and to contact their physician if early signs and symptoms of these reactions occur.
• The product information has been appropriately updated.
• Healthcare professionals are encouraged to report any suspected adverse reactions associated with the use of moxifloxacin.

Background

Moxifloxacin is known to impair liver function, and the product information was updated to include Stevens-Johnson-Syndrome (SJS) in 2002. A review of worldwide serious, including fatal, cases of both hepatotoxicity and bullous skin reactions such as SJS and toxic epidermal necrolysis (TEN) reported for moxifloxacin was recently performed.

Safety Concern

The liver injuries possibly related to moxifloxacin were more frequently of cholestatic or mixed hepatocellular-cholestatic than of hepatocellular type. Onset of symptoms was usually between 3 and 10 days. Isolated cases of delayed hepatotoxic effects were also identified and usually occurred 5 to 30 days after cessation of moxifloxacin therapy. Eight reports of fatal hepatic injuries were considered as possibly related to moxifloxacin therapy. Cases of positive re-challenge gave further evidence of a causal relationship. However, the majority of patients experiencing serious liver injuries where the outcome was reported improved or recovered.
TEN was reported in several cases where a causal relationship was considered possible; this included two cases with fatal outcome. Additionally, a total of 35 individual cases of SJS were reported, including three cases where there was a fatal outcome and seven cases which were considered life-threatening. In these 10 cases of severe SJS, a progression to TEN was documented in three patients.  Based on the large patient exposure, the incidence of both life threatening liver injuries and TEN is very low, although a definite frequency cannot be calculated from these reports.  As a consequence of this review, Bayer has revised the product information for moxifloxacin across the EU.

Recommendations to Healthcare Professionals

We would like to remind you that moxifloxacin is contraindicated in patients with impaired liver function (Child Pugh C) and in patients with transaminases increased > 5 fold ULN.  We would like to further remind you to be vigilant for the early signs and symptoms of severe liver injury and bullous skin reactions like SJS or TEN. Patients should be advised to stop treatment immediately and to contact a physician if relevant signs or symptoms occur, including rapidly developing asthenia associated with jaundice, dark urine, bleeding tendency and hepatic encephalopathy.  When prescribing moxifloxacin, consideration should be given to official guidance on the appropriate use of antibacterial agents which is especially relevant with regard to treatment of less severe infections.

Call for reporting

If you have observed similar cases, please report adverse reactions to the MHRA or to Bayer HealthCare.  Suspected adverse reactions should be reported directly to the MHRA via the Yellow Card Scheme (information can be found at Hwww.yellowcard.gov.ukH) or to Bayer HealthCare Drug Surveillance Department either by phone on 01635 563500, fax 01635 563703, by e-mail to Hphdsguk@bayer.co.ukH.

Communication information

If you have any further questions please do not hesitate to contact Bayer HealthCare Medical Information department on 01635 563116 or by e-mail at medical.science@bayer.co.uk.

Yours sincerely,
Medical Director
Bayer Schering Pharma, Bayer plc

Original "Dear Doctor Letter" can be viewed by clicking here
 

Use of Moxifloxacin (Avelox) severely restricted by the European Medicines Agency

FRANKFURT, July 24 (Reuters) - The European Medicines Agency has recommended limiting the use of oral moxifloxacin-containing medicines after finalizing a review of the safety of the antibiotics, the agency said on Thursday.

The European body (EMEA) said it had concluded that these drugs should only be prescribed for acute bacterial sinusitis, acute exacerbation of chronic bronchitis and community-acquired pneumonia when other antibiotics cannot be used or have failed.

"The agency also recommended strengthening the warnings for oral moxifloxacin medicines," it said in a statement.

Moxifloxacin, a fluoroquinolone antibiotic, is marketed by Bayer (BAYG.DE: Quote, Profile, Research) under its brand Avelox.

At its July 2008 meeting, the agency's Committee for Medicinal Products for Human Use (CHMP) concluded that the benefits of oral moxifloxacin medicines continued to outweigh its risks.

However, due to safety concerns, mainly related to an increased risk of adverse hepatic reactions, it recommended restricting their use in these indications.

The CHMP opinion will now be forwarded to the European Commission to apply to all oral moxifloxacin-containing medicines authorized in the European Union.

Responding to the recommendation, Bayer said the review confirmed the positive benefit-risk profile of the drug.

"We would welcome an EMEA assessment of other antibiotics used for treatment of these infections in a similar fashion in the interest of patient care," said Kemal Malik, a member of Bayer HealthCare executive committee and chief medical officer.

http://uk.reuters.com/article/governmentFilingsNews/idUKL2453307820080724


A copy of the ANTI-INFECTIVE DRUGS ADVISORY COMMITTEE 67TH MEETING (THURSDAY, OCTOBER 21, 1999) in which the severe adverse reactions to moxifloxacin were discussed is available by 'right clicking' on the following link and then selecting 'save target as' to save this PDF file to your desktop:

ANTI-INFECTIVE DRUGS ADVISORY COMMITTEE 67TH MEETING

The following is the text of pertinent portion of this meeting:

QUOTES FROM THE HEARING:

Committee Doc A: I'm going to say no, and I'm going to say no because of the following reasons. I think when the drug is marketed, no matter what kind of warning you put in it, it's going to be used in substantially different ways than it's been used in the trials. And, I think that this is exactly the kind of place that you get into trouble with, when a drug is approved, it's carefully studied in a trial, people are carefully excluded who have prolonged QT intervals, are carefully excluded who are on drugs that can be additive with it in terms of the effect, and it's used for a very short interval of time, and so it's not clear -- I am absolutely convinced that the drug will be used differently once it's marketed frequently. And, I think there are enough things that really haven't been answered. I don't know if the drug effects potassium and magnesium excretion, and whether it somehow is additive with other drugs that produces increased loss of electrolytes through the kidneys, because that has not been looked at. It seems to possibly cause or increase the incidence of atrial fibrillation, and we don't have real drug levels from real patients correlated with QT times.  So, I don't know, I'm just somewhat concerned. The other issue with safety, obviously, is the risk benefit ratio, and I'm not sure I see what this drug adds to drugs that we already have that's so unique that we need this drug, that we absolutely need it, and we need it now for some indication. There are other drugs that you can use. They may have the same problem, but given that they haven't been studied in this way, I don't know that's the case.------

COMMITTEE DOC B: Well, I guess I'd have to say no, the data on safety are not convincing. It seems to me, based on the discussion, that the QT facts are clinically relevant, steady state concentrations needs to be studied further. In addition, the concern about people using the drug for longer than 12 days, I don't think we have enough information on that, and I believe that that may occur, even though that probably would not necessarily be what we would recommend. The other concerns about other drugs that might prolong the QT interval, the problems with hypokalemia, the problems with death after the drug was discontinued, and, again, the age-old problem, the use of this drug in children, I think we need to study the drug and the pharmacokinetics, and we also need to study the safety in the pediatric population. We need data on that, because although it was not studied, and although it won't be approved for children, I'm afraid it will be used in this population and I'm concerned about that.----

COMMITTEE DOC C: I was prepared to vote for safety with an appropriate change in the label, but the two that have talked about all the things that we don't know about, you know, the behavior of this drug have swayed me. I think I shall have to vote against, I don't believe we know enough yet about  the safety because of the cardiac problems.----

Guest Expert Doc A: I was -- I thought Dr. A's summary captured a lot of my concerns, and I think that on balance we don't know enough now to conclude that it's safe.  I think the other thing that gives me pause is the fact that this is a drug that may be very widely used, so even if the estimates of one to two percent, which I think are very conservative, of meaningful QT prolongations are correct, that might be tens or hundreds of thousands of people who would experience those. So, it seems to me that knowing more would be necessary for me to say yes, so I think if I had a vote I would probably say no for now.----

ACTING CHAIRMAN : And finally, I'd like to make sure that there are no other comments that the voting members of the committee would like to make.----

Committee Doc D: I just have one comment, which also echoes a little bit what Dr. A said, which is that although I think this drug is safe, I think we also have to consider the other drugs, other antibiotics that are out there, and whether the risk benefit ratio is as good as other comparators or similar drugs that are there. And, I think in balance this probably doesn't add a terrible -- it doesn't add very much to the antibiotic armamentarium that we currently have.------

Dr. A: I'm a little confused by what we are voting on. I mean, my answer is still no from before. I agree that if the drug is approved that it has to have a warning label similar to what's been described. I also wonder whether it shouldn't include something about the possibility that it may induce atrial fibrillation in patients, particularly, patients at high risk for that arrhythmia. And, you know, whether it should contain information about the drug effect on QT may be aggravated by hypokalemia and, therefore, potassium levels, particularly, on patients who are on drugs that cause hypokalemia should be monitored, or at least baseline checked.  I mean, I think there may be other things that need to go into the warning label to caution people. I would also suggest that it say something about the fact that in the trials prolonged use of the drug, in terms of its cardiovascular safety, were not assessed, you know, by giving it longer than stated You know, in terms of the other drugs that have been approved, I guess one of the problems that the pharmaceutical company has here is that, you know, they were, perhaps, the first to come along, take a drug with this issue and evaluate it so thoroughly, so it's probably, you know, raised as many questions as it has answered.----

DR. A: Do you have data on how this drug affects potassium and magnesium excretion from the kidney? The second question, in terms of the accumulation of this drug in tissues, over what time period does that occur? What is the half life in tissues? Is it likely if people use the drug for longer periods of time that the drug would continue to accumulate and levels would continue to rise in tissues?----

DRUG CO. DOC: We do have some tissue accumulation studies in Phase I and Phase II and in small numbers of patients multiple time points. We also have a dialysis and skeletal muscle study. Most of those studies, however, were done with a single dose administration of very short term.  There is, as Dr. __showed you, considerable accumulation in pulmonary tissues which is helpful in this sort of setting. Our data for skeletal muscle is that the concentrations reached in skeletal muscle are about 80 percent of the plasma concentrations of the drug. We don't have data to address the possibility of long-term accumulation in tissues but for skeletal muscle the ratios are less than plasma concentrations.-----

So less than 8 weeks after this hearing where all these issues were raised, it was approved...(Bayer also makes Cipro)

http://www.fda.gov/ohrms/dockets/ac/99/transcpt/3558t2.rtf

Listed in Public Citizen as a DO NOT USE drug
 Numerous other, safer antibiotics are approved to treat the same infections as this drug

There are numerous FATAL adverse reactions associated with this drug. (Read More)

FRANKFURT, Feb 14 (Reuters) - Bayer (BAYG.DE: Quote, Profile, Research) is sending letters warning doctors in Europe of rare incidents of severe liver and skin side effects in patients taking its Avelox antibiotic, the German drugs and chemicals group said on Thursday.
Bayer has included the additional warnings in the packaging of Avelox products since autumn last year after some incidents of severe side effects were monitored, but is now reinforcing this by writing to doctors.
"The side effects are very rare. But when it happens, it is quite severe to patients. We want doctors to be more aware," said Yvonne Moeller, a spokeswoman at Bayer.
Avelox, one of Bayer's top-selling drugs, saw sales of almost 400 million euros ($584.4 million) in 2006.

© Reuters 2008 All rights reserved
 

Click here to read the Label Changes effective May 2007

Other adverse reactions associated with the fluoroquinolones

Peripheral Neuropathy
Cases of sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias and weakness have been reported in patients receiving quinolones.

QUINOLONES MAY HAVE THE POTENTIAL TO PROLONG THE QTc INTERVAL OF THE ELECTROCARDIOGRAM IN SOME PATIENTS. DUE TO THE LACK OF CLINICAL EXPERIENCE, QUINOLONES SHOULD BE AVOIDED IN PATIENTS WITH KNOWN PROLONGATION OF THE QTc INTERVAL, PATIENTS WITH UNCORRECTED HYPOKALEMIA, AND PATIENTS RECEIVING CLASS IA (E.G. QUINIDINE, PROCAINAMIDE) OR CLASS III (E.G. AMIODARONE, SOTALOL) ANTIARRHYTHMIC AGENTS.

Ruptures of the shoulder, hand, and Achilles tendons that required surgical repair or resulted in prolonged disability have been reported in patients receiving quinolones. Tendon rupture can occur during or after therapy with quinolones.

Quinolones may cause central nervous system (CNS) events including nervousness, agitation, insomnia, anxiety, nightmares, or paranoia.

As with other quinolones, disturbances of blood glucose, including symptomatic hyper- and hypoglycemia, have been reported, usually in diabetic patients receiving concomitant treatment with an oral hypoglycemic (e. g., glyburide) or with insulin. In these patients, the monitoring of blood glucose is recommended.

In 2004 new warning labels added to all of the Fluoroquinolones regarding Peripheral Neuropathy (irreversible nerve damage), Tendon Damage, Heart Problems (prolonged QT Interval / Torsades de pointes), Pseudomembranous colitis, Rhabdomyolysis (muscle wasting), Steven Johnson Syndrome, as well as concurrent usage of NSAIDs contributing to the severity of these reactions.
.
Although such events have been reported since the mid sixties, the FDA waited almost forty years to add such warnings to the package inserts.  These new warnings again fail to adequately warn either the patient or the physician.

"Drug companies write the package inserts of all drugs, carefully including the information they choose and
omitting information they want to avoid. Drug companies underwrite a large percentage of continuing
education courses for doctors. In doing so, they make sure that the speakers represent the company view.
Drug companies design studies that are meant to produce favorable results and then publish the studies in
medical journals. Studies with unfavorable results are not published. Drug reps typically bring stacks of
studies, all favorable, which impress doctors, who no longer have the time or motivation to search  the
medical literature themselves. Drug reps do not include independent studies with less favorable
conclusions. Many doctors never see these." 

Source:   THE MEDICAL PROFESSION AND THE CULTURE OF CORRUPTION

The following has been associated with fluoroquinolone therapy:

PERIPHERAL NEUROPATHY (as noted above)
Achilles and other tendon ruptures that required surgical repair or resulted in prolonged disability.
Convulsions, increased intracranial pressure, and toxic psychosis.
Central nervous system (CNS) events including: dizziness, confusion, tremors, hallucinations, depression, and, ly, suicidal thoughts or acts. These reactions may occur following the first dose.
Severe hypersensitivity reactions characterized by rash, fever, eosinophilia, jaundice, and hepatic necrosis with fatal outcome
Pseudomembranous colitis and may range in severity from mild to life-threatening.
Lameness in immature dogs with permanent lesions of the cartilage.
Central nervous system (CNS) events, including nervousness, agitation, insomnia, anxiety, nightmares or paranoia.
Crystalluria
Moderate to severe photoxicity

Pregnancy Warning

Fluoroquinolones caused fetal harm in animal studies, including decreased body weights and malformed bones as well as an increased risk of death. Because of the potential for serious adverse effects to the fetus, these drugs should not be used by pregnant women.

Breast-feeding Warning

Fluoroquinolones are excreted in human milk. Because of the potential for serious adverse effects in nursing infants, you should not take these drugs while nursing.

Additional adverse events reported:

Body as a Whole: Change in serum phenytoin.

Cardiovascular: Palpitation, atrial flutter, ventricular ectopy, syncope, hypertension, angina pectoris, myocardial infarction, cardiopulmonary arrest, cerebral thromobosis. Cardiovascular collapse, cardiopulmonary arrest, myocardial infarction, arrhythmia, tachycardia, palpitation, cerebral thrombosis, syncope, cardiac murmur, hypertension, hypotension, angina pectoris. Postural hypotension, vasculitis.

Central Nervous System: Dizziness, lightheadedness, insomnia, nightmares, hallucinations, manic reaction, irritability, tremor, ataxia, convulsive seizures, lethargy, drowsiness, weakness, malaise, anorexia, phobia, depersonalization, depression, paresthesia. Convulsive seizures, paranoia, toxic psychosis, depression, dysphasia, phobia, depersonalization, manic reaction, unresponsiveness, ataxia, confusion, hallucinations, dizziness, lightheadedness, paresthesia, anxiety, tremor, insomnia, nightmares, weakness, drowsiness, irritability, malaise, lethargy Agitation, confusion, delirium, dysphasia, myoclonus, nystagmus, toxic psychosis.
.
Gastrointestinal: Painful oral mucosa, oral candidiasis, dysphagia, intestinal perforation, gastrointestinal bleeding. Cholestatic jaundice has been reported. Ileus, jaundice, gastrointestinal bleeding, C. difficle associated diarrhea, pseudomembranous colitis, pancreatitis, hepatic necrosis, intestinal perforation, dyspepsia, epigastric or abdominal pain, vomiting, constipation, oral ulceration, oral candidiasis, mouth dryness, anorexia, dysphagia, flatulence Constipation, dyspepsia, flatulence, hepatic necrosis, jaundice, pancreatitis, pseudomembranous colitis. (The onset of pseudomembranous colitis symptoms may occur during or after antimicrobial treatment.)

Hemic/Lymphatic: Agranulocytosis, hemolytic anemia, methemaglobinemia, prolongation of prothrombin time

Metabolic/Nutritional: Elevation of serum triglycerides, cholesterol, blood glucose, serum potassium.

Musculoskeletal: Arthralgia or back pain, joint stiffness, achiness, neck or chest pain, flare up of gout. Arthralgia, jaw, arm or back pain, joint stiffness, neck and chest pain, achiness, flare up of gout Myalgia, possible exacerbation of myasthenia gravis, tendinitis/tendon rupture.

Renal/Urogenital: Interstitial nephritis, nephritis, renal failure, polyuria, urinary retention, urethral bleeding, vaginitis, acidosis. Renal failure, intarstitial nephritis, hemorrhagic cystitis, renal calcuti, frequent urination, acidosis, urethral bleeding, polyuria, urinary retention, gynecomastia, candiduria, vaginitis. Crystalluria, cylindruria, hematuria, and albuminutia have also been reported.
Albuminuria, candiduria, renal calculi, vaginal candidiasis.

Respiratory: Dyspnea, epistaxis, laryngeal or pulmonary edema, hiccough, hemophysis, bronchospasm, pulmonary embolism. Respiratory arrest, pulmonary embolism, dyspnea, pulmonary edema, respiratory distress, pleural effusion, hemoptysis, epistaxis, hiccough

Skin/Hypersensitivity: Pruritus, urticaria, photosensitivity, flushing, fever, chills, angioedema, edema of the face, neck, lips, conjunctivae or hands, cutaneous candidiasis, hyperpigmentation, erytherna nodosum. Allergic reactions ranging from urticaria to anaphylactic reactions have been reported. Anaphylactic reactions, erythema multiforme/Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis, vasculitis, angioedema, edema of the lips, face, neck, conjunctivae, hands or lower extremities, purpura, fever, chills, flushing, pruritus, urtigaria, cutaneous candidiasis, vesicles, increased perspiration, hyperpigmentation, erythema nodosum, photosensitivity. Allergic reactions ranging from urticaria to anaphylactic reactions have been reported. Anaphylactic reactions, erythema multiforme/Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis.

Special Senses: Blurred vision, disturbed vision (change in color perception, overbrightness of lights), decreased visual acuity, diplopia, eye pain, tinnitus, hearing loss, bad taste. Decreased visual acuity, blurred vision, disturbed vision (flashing lights, change in color perception, overbrightness of lights, diplopia), eye pain, anosmia, hearing loss, tinnitus, nystagmus, a bad taste. Also reported were agranulocytosis, prolongation of prothrombin time, and possible exacerbation of myasthenia gravis. anosmia, taste loss.
 

Adverse Laboratory Changes

Oral

Changes in Laboratory Parameters Listed as Adverse Events:

Hepatic: Elevations of ALT (SGPT), AST (SGOT), alkaline phosphatase , LDH , serum bilirubin.
Hematologic: Eosinophilia, leukopenia, decreased blood platelets, elevated blood platelets, pancytopenia.

Renal: Elevations of serum creatinine, BUN, CRYSTALLURIA, CYLINDRURIA, AND HEMATURIA HAVE BEEN REPORTED.

Other Changes: Elevation of serum gammaglutamyl transferase, elevation of serum amylase, reduction in blood glucose, elevated uric acid, decrease in hemoglobin, anemia, bleeding diathesis, increase in blood monocytes, leukocytosis.

I.V.

The most frequently reported changes in laboratory parameters with intravenous fluoroquinolone therapy:

Hepatic: Elevations of AST (SGOT), ALT (SGPT), alkaline phosphatase, LDH, and serum bilirubin.
Hematologic: Elevated eosinophil and platelet counts, decreased platelet counts, hemoglobin and/or hematocrit.

Renal: Elevations of serum creatinine, BUN, and uric acid.

Other: Elevations of serum creatinine, phosphokinase, serum theophylline (in patients receiving theophylline concomitantly), blood glucose, and triglycerides.

Other changes occurring infrequently were: decreased leukocyte count, elevated atypical lymphocyte count, immature WBCs, elevated serum calcium, elevation of serum gamma-glutamyl transpeptidose ( GI), decreased BUN, decreased uric acid, decreased total serum protein, decreased serum albumin, decreased serum potassium, elevated serum potassium, elevated serum cholesterol.

Other changes occurring ly during administration of fluoroquinolone were: elevation of serum amylase, decrease of blood glucose, pancytopenia, leukocytosis, elevated sedimentation rate, change in serum phenytoin, decreased prothrombin time, hemolytic anemia, and bleeding diathesis.
 

ANIMAL PHARMACOLOGY
Oral and I.V.

“Fluoroquinolone and other quinolones have been shown to cause arthropathy in immature animals of most species tested. …Damage of weight bearing joints was observed in juvenile dogs and rats. In young beagles, 100 mg/kg ciprofloxacin, given daily for 4 weeks, caused degenerative articular changes of the knee joint… In a subsequent study in beagles, removal of weight bearing from the joint reduced the lesions but did not totally prevent them.”
Source: www.rxlist.com

“Crystalluria, sometimes associated with secondary nephropathy, occurs in laboratory animals dosed with fluoroquinolone….In rhesus monkeys, crystalluria without nephropathy has been noted after single oral doses as low as 5 mg/kg…In dogs, ciprofloxacin at 3 and 10 mg/kg by rapid IV injection (15 sec.) produces pronounced hypotensive effects…In rhesus monkeys, rapid IV injection also produces hypotension but the effect in this species is inconsistent and less pronounced.”
Source: www.rxlist.com

“In mice, concomitant administration of nonsteroidal anti-inflammatory drugs such as phenylbutazone and indomethacin with quinolones has been reported to enhance the CNS stimulatory effect of quinolones."
Source: www.rxlist.com

"Ocular toxicity seen with some related drugs has not been observed in ciprofloxacin-treated animals.”
Source: www.rxlist.com

All brand names are trademarks of their respected manufacturers.  The information being provided above is to be considered a quick reference guide.  For complete information please view the complete package insert at www.rxlist.com